The eukaryotic translation initiation factor 3 subunit L protein interacts with FlavivirusNS5 and may modulate yellow fever virus replication

Morais, Ana Theresa Silveira de; Terzian, Ana Carolina Bernardes; Duarte, Danilo V.B.; Bronzoni, Roberta V.B.; Madrid, Maria Carolina Ferrari Sarkis; Gavioli, Arieli F.; Gil, Laura Helena Vega Gonzales; Oliveira, Amanda G.; Zanelli, Cleslei Fernando; Valentini, Sandro Roberto; Rahal, Paula; Nogueira, Maurício Lacerda

doi:10.1186/1743-422x-10-205

Cited by 19 publications

(20 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is surprising since eIF3 together with the 40S ribosomal subunit, also under-represented in the present study, have been shown to be important during the initial phase of protein synthesis, and flaviviruses are thought to prevent host cell protein shutoff, at least in mammalian cells [ 149 ]. However, a recent study using yellow fever virus (YFV) in mammalian cells found that NS5 interacts with eIF3L, a subunit of eIF3, and that overexpression of this subunit facilitates YFV translation but does not affect global protein synthesis [ 150 ]. This suggests that eIF3 is also important in tick cells for replication of flaviviruses but that down-regulation of this initiation factor might have an antiviral effect.…”

Section: Resultsmentioning

confidence: 99%

Ixodes scapularis and Ixodes ricinus tick cell lines respond to infection with tick-borne encephalitis virus: transcriptomic and proteomic analysis

et al. 2015

View full text Add to dashboard Cite

BackgroundIxodid ticks are important vectors of a wide variety of viral, bacterial and protozoan pathogens of medical and veterinary importance. Although several studies have elucidated tick responses to bacteria, little is known about the tick response to viruses. To gain insight into the response of tick cells to flavivirus infection, the transcriptomes and proteomes of two Ixodes spp cell lines infected with the flavivirus tick-borne encephalitis virus (TBEV) were analysed.MethodsRNA and proteins were isolated from the Ixodes scapularis-derived cell line IDE8 and the Ixodes ricinus-derived cell line IRE/CTVM19, mock-infected or infected with TBEV, on day 2 post-infection (p.i.) when virus production was increasing, and on day 6 p.i. when virus production was decreasing. RNA-Seq and mass spectrometric technologies were used to identify changes in abundance of, respectively, transcripts and proteins. Functional analyses were conducted on selected transcripts using RNA interference (RNAi) for gene knockdown in tick cells infected with the closely-related but less pathogenic flavivirus Langat virus (LGTV).ResultsDifferential expression analysis using DESeq resulted in totals of 43 and 83 statistically significantly differentially-expressed transcripts in IDE8 and IRE/CTVM19 cells, respectively. Mass spectrometry detected 76 and 129 statistically significantly differentially-represented proteins in IDE8 and IRE/CTVM19 cells, respectively. Differentially-expressed transcripts and differentially-represented proteins included some that may be involved in innate immune and cell stress responses. Knockdown of the heat-shock proteins HSP90, HSP70 and gp96, the complement-associated protein Factor H and the protease trypsin resulted in increased LGTV replication and production in at least one tick cell line, indicating a possible antiviral role for these proteins. Knockdown of RNAi-associated proteins Argonaute and Dicer, which were included as positive controls, also resulted in increased LGTV replication and production in both cell lines, confirming their role in the antiviral RNAi pathway.ConclusionsThis systems biology approach identified several molecules that may be involved in the tick cell innate immune response against flaviviruses and highlighted that ticks, in common with other invertebrate species, have other antiviral responses in addition to RNAi.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-1210-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Ixodes scapularis and Ixodes ricinus tick cell lines respond to infection with tick-borne encephalitis virus: transcriptomic and proteomic analysis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Viruses may have evolved stimulation mechanisms that synthesize ribosomal proteins to facilitate the translation of their viral components. Moreover, the PPI analysis showed interaction of the RPL/S with EIF3L, POLR2H, and GTF2F2, which have been also implicated in viral replication [69,70,71]. However, we previously described that VHSV replication appeared to be halted in rainbow trout RBCs early after exposure ex vivo [13].…”

Section: Discussionmentioning

confidence: 99%

Integrated Transcriptomic and Proteomic Analysis of Red Blood Cells from Rainbow Trout Challenged with VHSV Point Towards Novel Immunomodulant Targets

et al. 2019

View full text Add to dashboard Cite

Teleost red blood cells (RBCs) are nucleated and therefore can propagate cellular responses to exogenous stimuli. RBCs can mount an immune response against a variety of fish viruses, including the viral septicemia hemorrhagic virus (VHSV), which is one of the most prevalent fish viruses resulting in aquaculture losses. In this work, RBCs from blood and head kidney samples of rainbow trout challenged with VHSV were analyzed via transcriptomic and proteomic analyses. We detected an overrepresentation of differentially expressed genes (DEGs) related to the type I interferon response and signaling in RBCs from the head kidney and related to complement activation in RBCs from blood. Antigen processing and presentation of peptide antigen was overrepresented in RBCs from both tissues. DEGs shared by both tissues showed an opposite expression profile. In summary, this work has demonstrated that teleost RBCs can modulate the immune response during an in vivo viral infection, thus implicating RBCs as cell targets for the development of novel immunomodulants.

show abstract

“…The eIF3l subunit was found to interact with the Flavivirus NS5 and eIF3l overexpression was suggested to promote Flavivirus translation and thus to modulate the yellow fever virus replication cycle ( 145 ). Depletion of endogenous eIF3k de-sensitized simple epithelial cells to various types of apoptotic stimuli and promoted the retention of active caspase 3 in cytoplasmic inclusions by increasing Cas3 binding to keratins ( 146 ).…”

Section: Eif3 In Human Health and Diseasementioning

confidence: 99%

Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle

Valášek¹,

Zeman²,

Wagner³

et al. 2017

Nucleic Acids Research

112

138

View full text Add to dashboard Cite

Protein synthesis is mediated via numerous molecules including the ribosome, mRNA, tRNAs, as well as translation initiation, elongation and release factors. Some of these factors play several roles throughout the entire process to ensure proper assembly of the preinitiation complex on the right mRNA, accurate selection of the initiation codon, errorless production of the encoded polypeptide and its proper termination. Perhaps, the most intriguing of these multitasking factors is the eukaryotic initiation factor eIF3. Recent evidence strongly suggests that this factor, which coordinates the progress of most of the initiation steps, does not come off the initiation complex upon subunit joining, but instead it remains bound to 80S ribosomes and gradually falls off during the first few elongation cycles to: (1) promote resumption of scanning on the same mRNA molecule for reinitiation downstream—in case of translation of upstream ORFs short enough to preserve eIF3 bound; or (2) come back during termination on long ORFs to fine tune its fidelity or, if signaled, promote programmed stop codon readthrough. Here, we unite recent structural views of the eIF3–40S complex and discus all known eIF3 roles to provide a broad picture of the eIF3’s impact on translational control in eukaryotic cells.

show abstract

The eukaryotic translation initiation factor 3 subunit L protein interacts with FlavivirusNS5 and may modulate yellow fever virus replication

Cited by 19 publications

References 31 publications

Ixodes scapularis and Ixodes ricinus tick cell lines respond to infection with tick-borne encephalitis virus: transcriptomic and proteomic analysis

Ixodes scapularis and Ixodes ricinus tick cell lines respond to infection with tick-borne encephalitis virus: transcriptomic and proteomic analysis

Integrated Transcriptomic and Proteomic Analysis of Red Blood Cells from Rainbow Trout Challenged with VHSV Point Towards Novel Immunomodulant Targets

Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle

Contact Info

Product

Resources

About